Analysis of hyperplastic foci in livers with hepatocellular carcinomas by flow cytometry and AgNOR staining

The phase S ratlo in cell cycles were analyzed in livers with hyperplastic foci (HPF) and in livers without HPF by nuclear DNA determinatlons using flow cytometry, and by stalning wlth argyrophilic protelns of the nucieolar organlzer reglon (AgNOR). Flow cytometric analysis was done on 50 fresh frozen speclmens of livers resected from 50 patients wlth hepatocellular carcinoma (HCC). Paraffin sections from the same patients were analyzed uslng AgNOR staining. There were 25 cases each wlth and without HPF. We examined the stage of fibrosis and the grade of inflammatory activity according to the modlfied Scheuer and Desmet scale. The incidence of HCC recurrence among these patlents was also studied. The average phase S ratio of the livers of the patients with HPF was 6.5+3.2%, and that of the livers of the patients without HPF was 4.0±2.5%. The ratio differed slgnificantly between the two groups (P<0.01). The average AgNOR score for HPF lesions of the HPF‐positlve cases was 1.6020.34, that for non‐HPF lesions In the HPF‐positive cases was 1.2920.12, and that for the HPF‐negative cases was 1.1920.14. Significant differences were found between the average AgNOR scores for HPF lesions of the HPF‐posltive cases and the non‐HPF lesions of the HPF‐posltive cases (P<0.0l), as well as between the non‐HPF lesions in the HPF‐positive cases and the HPF‐negatlve cases (P‐cO.05). Severe fibrosis (stage 3) and cirrhosls (stage 4) were found In 76% of HPF‐positive cases and 48% of HPF‐negatlve cases. The llvers of HPF‐posltlve patlents were slgnificantiy more cirrhotic than those of HPF‐negative patients (R0.05). The association between HPF and the Inflammatory grade was not slgnlficant (Ao.05). The incldence of HCC recurrence among HPF‐positive cases was significantly higher than that among the HPF‐negative cases (P<0.05). The average phase S ratio of the recurrent HPF‐positive patients was 7.48+3.48%, slgnlficantly higher than that of HPF negative cases (5.57*3.06%, Pc0.05). Hyperplastic foci of the llver was shown to be a hlghly prollferatlve lesion. The proliferative activity of the non‐HPF lesions in the HPF‐positive patients was also higher than that of the HPF‐negative patients. Hyperplastic focl tended to be present in cirrhotic livers, but it was not associated wlth the grade of inflammatory activlty of the Iiver. Hyperplastic focl may represent an important predictor of recurrence after hepatic resection.